PROJECT-003: MOLECULAR BIOLOGY AND CANCER GENETICS PROGRAM (MBCG) PROJECT SUMMARY / ABSTRACT The Molecular Biology & Cancer Genetics (MBCG) Program at The Ohio State University Comprehensive Cancer Center (OSUCCC), led by Michael Ostrowski, PhD and Matthew Ringel, MD, unites a highly productive, collaborative and cancer focused team of 44 basic and translational scientists representing 7 colleges and 18 academic departments at The Ohio State University. Program science is centered in four major cancer-focused scientific themes: small non-coding RNAs and cancer, human cancer genetics/genomics, signal transduction and therapeutic resistance, and tumor microenvironment. Program members utilize state-of-the-art approaches to 1) identify genes and pathways that fuel tumor cell initiation and growth, and 2) provide mechanistic details of how these genes and pathways contribute to tumor progression and therapeutic resistance. Our overall goal is to define the mechanisms that account for the association between genes and cancer and to exploit this knowledge in order to reduce the incidence of death from cancer. The Specific Aims of the MBCG Program are: 1) to identify human genes, including non-coding genes such as those encoding microRNAs, that either through direct mutations or epigenetic mechanisms, result in an increased predisposition to cancer; 2) to determine the molecular mechanisms underlying the expression and function of the genes contributing to normal development, cancer progression, and therapeutic resistance; 3) to utilize the knowledge gained from gene identification and gene functions in tumorigenesis in order to reduce the incidence of death from cancer. During the prior funding period of the OSUCCC P30 CCSG, MBCG Program members published 810 research papers, including 104 high impact (> 10) manuscripts in journals such as Cell, Cancer Cell, Science, Nature Medicine, Nature Cell Biology, Journal of Clinical Oncology, and Journal of Clinical Investigation. There is extensive collaboration, with 21% intra-programmatic, 31% inter-programmatic, and 66% multi- institutional publications. Overall, 81% of MBCG publications are collaborative. MBCG Program members are principal investigators (PIs) on seven NCI programmatic grants, including a P01 and U01 in breast cancer (P01 CA097189, U01 CA154200), a P01 and P50 SPORE in thyroid cancer (P01 CA124570, P50 CA168505), a P01 in epigenetics (CA129242) and two U01s in lung cancer (U01 CA152758, U01 CA166905). They are PIs on CCSG-approved grants whose direct funding is currently $9.39 million, with $7.5 million in NCI funding (80% of total CCSG-approved funding). Program members are principal investigators on 21 active protocols that have accrued 5760 patients over the past five years. MBCG studies are predominantly interventional but non-therapeutic, and non-interventional as most of our interventional therapeutic work is accomplished collaboratively within the Translational Therapeutics and Leukemia Research Programs.